Engineering the alternative oxidase gene to better understand and counteract mitochondrial defects: state of the art and perspectives

Br J Pharmacol. 2014 Apr;171(8):2243-9. doi: 10.1111/bph.12570.

Abstract

Mitochondrial disorders are nowadays recognized as impinging on most areas of medicine. They include specific and widespread organ involvement, including both tissue degeneration and tumour formation. Despite the spectacular progresses made in the identification of their underlying molecular basis, effective therapy remains a distant goal. Our still rudimentary understanding of the pathophysiological mechanisms by which these diseases arise constitutes an obstacle to developing any rational treatments. In this context, the idea of using a heterologous gene, encoding a supplemental oxidase otherwise absent from mammals, potentially bypassing the defective portion of the respiratory chain, was proposed more than 10 years ago. The recent progress made in the expression of the alternative oxidase in a wide range of biological systems and disease conditions reveals great potential benefit, considering the broad impact of mitochondrial diseases. This review addresses the state of the art and the perspectives that can be now envisaged by using this strategy.

Keywords: allospecific gene expression; alternative oxidase; mitochondrial diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genetic Engineering / methods*
  • Humans
  • Mitochondria / enzymology
  • Mitochondria / genetics*
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / physiopathology
  • Mitochondrial Diseases / therapy*
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / physiology
  • Mitochondrial Proteins / therapeutic use*
  • Oxidoreductases / genetics*
  • Oxidoreductases / physiology
  • Oxidoreductases / therapeutic use*
  • Plant Proteins / genetics*
  • Plant Proteins / physiology
  • Plant Proteins / therapeutic use*

Substances

  • Mitochondrial Proteins
  • Plant Proteins
  • Oxidoreductases
  • alternative oxidase